Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of macrophage migration inhibitory factor (MIF), a proinflammatory and carcinogenic cytokine, were significantly higher in the sera from patients with hepatocellular carcinoma (HCC; 25.6+/-15.3 ng/ml, n=55) and liver cirrhosis (LC; 18.9+/-10.7 ng/ml, n=26) compared with sera from patients with gastrointestinal cancer (6.8+/-7.5 ng/ml, n=29) and normal controls (5.6+/-1.2 ng/ml, n=45; P<0.01). Hepatocytes from patients with LC and HCC, but not from chronic hepatitis, expressed very high levels of MIF. A possible association between overexpression of MIF and hepatocarcinogenesis is suggested.
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PMID:Macrophage migration inhibitory factor in hepatocellular carcinoma and liver cirrhosis; relevance to pathogenesis. 1152 May 95

Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine involved in inflammation and immune responses as well as in growth factor-dependent cell proliferation, cell cycle, angiogenesis, and tumorigenesis. Several studies have documented MIF expression in the sera following hepatic resection or in the course of liver cancer progression, but there is a paucity of information regarding the effect of MIF on hepatoma cells and relating mechanisms. In this paper, by [3H] thymidine incorporation, we found that exogenously added MIF could promote the proliferation of HepG2 in a dose-dependent manner. Hepatopoietin (HPO), as a liver-specific regeneration augmenter, could be induced by the expression of MIF in hepatoma cells. The activity of HPO promoter was increased, and its levels were enhanced after MIF was overexpressed in hepatoma cells. The similarities between HPO and MIF in structure and action led us to investigate their interaction and the inducing biological significance. Using yeast two-hybrid identification, we found that HPO interacted with MIF in yeast cells, and their binding ability was higher than that between HPO and JAB1 (Jun activation domain binding protein) or MIF and JAB1 in yeast cells. Their interaction was further verified by His pull-down assay in vitro and coimmunoprecipitation experiment in vivo. They were colocalized in the cytoplasm. Both HPO and MIF could bind to JAB1 and modulate the AP-1 pathway. When HPO and MIF were cotransfected into HepG2 cells, the binding activity of MIF to JAB1 was reduced, and the activity of AP-1 was improved. In contrast, MIF overexpressed in HepG2 was unable to interfere with the binding activity of HPO to JAB1, but its potentiation on AP-1 activity was reduced significantly. Taken together, these results indicate that MIF plays an important role in the proliferation of hepatoma cells, and the effect of MIF is in concert with HPO.
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PMID:Macrophage migration inhibitory factor directly interacts with hepatopoietin and regulates the proliferation of hepatoma cell. 1547 2

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that controls inflammatory processes, and inflammation is known to play an important role in the pathogenesis of atrial fibrillation (AF). The present study sought to investigate whether MIF expression is responsible for the changes in L-type Ca2+ currents (I(Ca,L)) seen in AF. Whole-cell voltage-clamp recordings and biochemical assays were used to study the regulation and expression of I(Ca,L) in human atrial myocytes and in HL-1 cells. Basal I(Ca,L) was reduced in AF compared to sinus rhythm (SR) controls, mRNA and protein levels of the pore-forming alpha1C subunit of L-type Ca2+ channel (LCC alpha1C) were also decreased, while MIF expression levels were increased in AF. Levels of Src and activated Src (p-Src Y416) were higher in AF than in SR. Treatment of atrial myocytes from a patient with SR with human recombinant MIF (rMIF) (40 nM, 1 h) was found to depress I(Ca,L) amplitudes, while mouse rMIF (20 or 40 nM, 24 h) suppressed peak I(Ca,L) in HL-1 cells by approximately 69% and approximately 83% in a concentration-dependent manner. Mouse rMIF impaired the time-dependent recovery from inactivation of I(Ca,L) and down-regulated LCC alpha1C subunit levels. The depression of I(Ca,L) and decrease of LCC protein levels induced by rMIF were prevented by the Src inhibitors genistein and PP1. These results implicate MIF in the electrical remodeling that accompanies AF, probably by decreasing I(Ca,L) amplitudes through impairment of channel function, down-regulation of LCC alpha1C subunit levels, and the activation of c-Src kinases in atrial myocytes.
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PMID:Involvement of Src in L-type Ca2+ channel depression induced by macrophage migration inhibitory factor in atrial myocytes. 1974 92

Macrophage migration inhibitory factor (MIF) has emerged to play a central role in the control of the host inflammatory and immune response. Several reports have documented that MIF can inactivate the tumor suppresser activity of p53; overexpression of MIF was significantly higher in both the sera and the local lesions from patients with HCC than from patients with normal controls. These findings indicate that MIF may contribute to multiple aspects of tumor progression and neoplasia, thus MIF may be an effective therapeutic target molecule. We speculate that MIF is important for the development and progression of hepatocellular carcinoma, and can be used as a marker for tumor detection.
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PMID:Macrophage migration inhibitory factor plays a pivotal role in hepatocellular carcinoma and may be a noninvasive imaging target. 2067 66

The aim of the present study was to investigate the expression of vascular endothelial growth factor (VEGF) and macrophage migration inhibitory factor (MIF) in HCC progression and their correlation with clinicopathological factors as well as the relationship between their expression levels. The expression of serum VEGF and MIF was evaluated in 150 patients with HCC and in 30 normal volunteers by enzyme-linked immunosorbent assay (ELISA). VEGF and MIF expression levels were evaluated by immunohistochemistry on tissue microarrays containing 150 HCCs with paired adjacent non-cancer liver tissues. VEGF and MIF mRNA levels were determined by quantitative PCR in another 48 HCCs. The correlation of VEGF and MIF with clinicopathological factors was analyzed in HCC. Serum VEGF and MIF concentrations were higher in HCC patients than the levels in the controls. The expression levels of VEGF and MIF in the HCC tissues were both higher than those in the adjacent non-tumor liver tissues. Overexpression of VEGF and MIF was significantly associated with tumor size (P=0.027 and 0.022, respectively), intrahepatic metastasis (P=0.032 and 0.027, respectively), vascular invasion (P=0.044 and 0.039, respectively) and TNM stage (P=0.028 and 0.013, respectively). Furthermore, VEGF and MIF mRNA levels were higher in HCC compared to levels in the paired non-cancer liver tissues. VEGF and MIF mRNA levels were correlated with tumor stage and metastasis. The expression of VEGF was positively related with MIF expression in HCC. The expression of MIF and VEGF in HCC was markedly positively correlated, which suggests that MIF and VEGF play an important role in the progression of HCC. Both factors may concomitantly accelerate the progression of HCC.
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PMID:Significance of the vascular endothelial growth factor and the macrophage migration inhibitory factor in the progression of hepatocellular carcinoma. 2436 6

Viral hepatitis is the most significant predisposing factor for hepatocellular carcinoma (HCC). Liver cancer grows silently with mild or no symptoms until the disease is advanced and with little hope of cure. Early recognition of the onset of HCC would help to select more effective therapies for patients leading to a better prognosis and life span. The current study aims to evaluate two diagnostic and prognostic markers - Prothrombin induced by vitamin K absence-II (PIVKA-II) and macrophage migration inhibitory factor (MIF) in the serum of patients with HCC and those with a high risk of developing hepatic cancers. Serum samples from hepatocellular carcinoma, hepatitis C and normal subjects were subjected to quantitative determinations of different parameters including alpha-fetoprotein (AFP), PIVKA-II and MIF. Significant differences between the various groups were recorded. PIVKA-II and AFP showed a higher specificity and sensitivity compared to MIF, and there was considerable correlation between AFP and both PIVKA and MIF. It is concluded that analysis of PIVKA-II and AFP can serve as useful non-invasive markers for the early detection of HCC with good sensitivity and specificity.
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PMID:Evaluation of serum PIVKA-II and MIF as diagnostic markers for HCV/HBV induced hepatocellular carcinoma. 2544 65

Objective To investigate the regulatory effect of miR-451a on macrophage migration inhibitory factor (MIF) and its effect on the proliferation of hepatocellular carcinoma HepG2 cells. Methods Real-time quantitative PCR was utilized to detect the expression of miR-451a and MIF mRNA in clinical liver cancer tissues. The luciferase reporter system was used to validate the regulatory relationship between miR-451a and MIF. The lentivirus overexpression vector of miR-451a was packaged to infect HepG2 cells. The expression of miR-451a and MIF mRNA was detected by real-time quantitative PCR. MIF protein level was detected by Western blotting. Cell proliferation was examined by MTT assay. Cell colony formation rate was tested by flat-plate colony formation experiment. Results The level of miR-451a was low and MIF mRNA was higher in liver cancer tissues. The luciferase reporter system showed that the intensity of the fluorescent signal was clearly weaker in MIF 3'UTR wild-type co-transfected cells with miR-451a mimics as compared with the other transfection groups. When HepG2 cells were infected with the lentivirus over-expressing miR-451a, the expression of miR-451a significantly increased; the expression of MIF significantly decreased; the cell proliferation and colony formation ability were weakened. Conclusion Overexpression of miR-451a can inhibit cell proliferation and colony formation by inhibiting MIF expression in HepG2 cells.
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PMID:[Overexpression of miR-451a inhibits cell proliferation by targeted macrophage migration inhibitory factor in HepG2 cells]. 3062 75